Tohoku J. Exp. Med., 2008, 215(3)

Atrial Natriuretic Peptide Attenuates Ischemia/Reperfusion-Induced Renal Injury by Reducing Neutrophil Activation in Rats

KOUSUKE CHUJO,¹ MASAAKI UEKI,¹ TAKEHIKO ASAGA¹ and SATOSHI TAIE¹

¹Department of Anesthesiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

Activated neutrophils have been implicated in the development of ischemia/reperfusion (I/R)-induced renal failure. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a major factor in acute inflammation, is responsible for the activation of neutrophils and for neutrophil chemotaxis to sites of injury. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators. We examined whether the human form of ANP attenuates I/R-induced renal injury by reducing neutrophil activation in a rat model. Male Wistar rats weighing 200-240 g were observed for 24 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (α-hANP, 0.2 μg/kg/min) beginning immediately after ischemia and continuing for 2 h after reperfusion. CINC-1 and myeloperoxidase (MPO) concentrations were measured to assess activation of the infiltrating neutrophil. Blood urea nitrogen and serum creatinine and urinary N-acetyl β-d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. α-hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. α-hANP also reduced I/R-induced increases in the concentrations of blood urea nitrogen and serum creatinine, and improved histopathologic changes, including acute tubular necrosis. These findings indicate that α-hANP attenuates I/R-induced acute renal injury, at least in part by reducing neutrophil activation, and may be useful in surgeries, associated with renal ischemia, as well as in renal transplantation.

keywords —— human atrial natriuretic peptide; neutrophils; kidney; ischemia/reperfusion; cytokine-induced neutrophil chemoattractant-1.

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 215, 257-266

Correspondence: Masaaki Ueki, Department of Anesthesiology, Faculty of Medicine, Kagawa University 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

e-mail: mueki@med.kagawa-u.ac.jp